In vitro hypoxia and excitotoxicity in human brain induce calcineurin-Bcl-2 interactions
Neuroscience, vol.117, no.3, pp.557-565, 2003 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 117 Issue: 3
- Publication Date: 2003
- Doi Number: 10.1016/s0306-4522(02)00934-x
- Journal Name: Neuroscience
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Page Numbers: pp.557-565
- Keywords: Aglycia, Bcl-2, Calcineurin, Hypoxia, Ischemia
- Akdeniz University Affiliated: No
Abstract
Although pathogenesis of neuronal ischemia is incompletely understood, evidence indicates apoptotic neuronal death after ischemia. Bcl-2, an anti-apoptotic and neuroprotective protein, interacts with calcineurin in non-neuronal tissues. Activation of calcineurin, which is abundant in the brain, may play a role in apoptosis. Using co-immunoprecipitation experiments in biopsy-derived, fresh human cortical and hippocampal slices, we examined possible interactions between calcineurin and Bcl-2. Calcineuin-Bcl-2 interactions increased after exposure in vitro to excitotoxic agents and conditions of hypoxia/aglycia. This interaction may shuttle calcineurin to substrates such as the inositol-1,4,5-tris-phosphate receptor because under these experimental conditions interactions between calcineurin and inositol-1,4,5-tris-phosphate receptor also increased. A specific calcineurin inhibitor, FK-520, attenuated insult-induced increases in calcineurin-Bcl-2 interactions and augmented caspase-3 like activity. These data suggest that Bcl-2 modulates neuroprotective effects of calcineurin and that calcineurin inhibitors increase ischemic neuronal damage. © 2003 IBRO. Published by Elsevier Science Ltd. All rights reserved.